In order to seek novel technetium-99m folate receptor-targeting agents, two folate derivatives (CN5FA and CNPFA) were synthesized and radiolabeled to obtain [^99mTc]Tc-CN5FA and [^99mTc]Tc-CNPFA complexes, which exhibited high radiochemical purity (>95%) without purification, hydrophilicity, and good stability in vitro. The KB cell competitive binding experiments indicated that [^99mTc]Tc-CN5FA and [^99mTc]Tc-CNPFA had specificity to folate receptor. Biodistribution studies in KB tumor-bearing mice illustrated that [^99mTc]Tc-CN5FA and [^99mTc]Tc-CNPFA had specific tumor uptake. Compared with [^99mTc]Tc-CN5FA, the tumor/muscle ratios of [^99mTc]Tc-CNPFA were higher, resulting in a better SPECT/CT imaging background. According to the results, the two ^99mTc complexes have potential as tumor imaging agents to target folate receptors.

To develop a novel ^99mTc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, n = 5–9) with different carbon linkers were designed, synthesized and radiolabeled with the [^99mTc]Tc(I)⁺ core, [^99mTc][Tc(I)(CO)₃(H₂O)₃]⁺ core and [^99mTc][Tc(V)N]²⁺ core. All the complexes are hydrophilic, maintain good stability and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection and sterile inflammation demonstrated that [^99mTc]Tc-CN5UBI 29-41 was able to distinguish bacterial infection from sterile inflammation, which had an improved abscess uptake and a greater target-to-nontarget ratio. SPECT imaging study of [^99mTc]Tc-CN5UBI 29-41 in bacterial infection mice showed that there was a clear accumulation in the infection site, suggesting that this radiotracer could be a potential radiotracer for bacterial infection imaging.

In order to seek novel technetium-99m bacterial infection imaging agents, a ciprofloxacin xanthate (CPF2XT) was synthesized and radiolabeled with [^99mTcN]²⁺ core to obtain the ^99mTcN-CPF2XT complex, which exhibited high radiochemical purity, hydrophilicity, and good stability in vitro. The bacteria binding assay indicated that ^99mTcN-CPF2XT had specificity to bacteria. A study of biodistribution in mice showed that ^99mTcN-CPF2XT had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses, indicating that it could distinguish bacterial infection from sterile inflammation. Compared to ^99mTcN-CPFXDTC, the abscess/blood and abscess/muscle ratios of ^99mTcN-CPF2XT were higher and the uptakes of ^99mTcN-CPF2XT in the liver and lung were obviously decreased. The results suggested that ^99mTcN-CPF2XT would be a potential bacterial infection imaging agent.

When developing novel radiopharmaceuticals, a linker moiety between the chelator and targeting vector can have a crucial influence on adjusting the affinity of the tracer and its biodistribution in organisms. To develop novel ^99mTc-labelled hypoxia imaging radiotracers, in this study, five isocyanide-containing 2-nitroimidazole derivatives with different linkers (L1, L2, L3, L4 and L5) were synthesised and radiolabelled with technetium-99m to obtain five stable ^99mTc-complexes ([^99mTc]Tc-L1, [^99mTc]Tc-L2, [^99mTc]Tc-L3, [^99mTc]Tc-L4 and [^99mTc]Tc-L5). Corresponding rhenium analogues of [^99mTc]Tc-L1 were synthesised and suggested the structures of these ^99mTc-complexes would be a monovalent cation with a technetium (I) core surrounded by six ligands. [^99mTc]Tc-L1 is hydrophilic, while the lipophilicities of [^99mTc]Tc-L2, [^99mTc]Tc-L3, [^99mTc]Tc-L4 and [^99mTc]Tc-L5 are close. In vitro cell experiments showed that all five novel ^99mTc-complexes had higher uptake in hypoxic cells compared with aerobic cells, which indicates the complexes have good hypoxia selectivity. The biodistribution of the five ^99mTc-complexes in S180 tumour-bearing mice showed that they all had certain uptake in the tumours. Among them, [^99mTc]Tc-L1 had the highest tumour-to-muscle (4.68 ± 0.44) and tumour-to-blood (3.81 ± 0.46) ratios. The introduction of polyethylene glycol (PEG) chains effectively reduced the lipophilicity and decreased uptake by the liver, intestine and blood but also increased clearance from the tumours. In vivo metabolic studies showed [^99mTc]Tc-L1 kept intact and remained stable in tumour, blood and urine at 2 h post-injection. The results of SPECT imaging showed that [^99mTc]Tc-L1 had significant tumour uptake at 2 h post-injection, but there was still high uptake in abdominal organs such as the liver and kidney, suggesting that this complex needs to be further optimised before being used for tumour hypoxia imaging.

To develop potential technetium-99m single-photon emission computed tomography (SPECT) imaging agents for bacterial infection imaging, the novel norfloxacin isonitrile derivatives CN4NF and CN5NF were synthesized and radiolabeled with a [^99mTc][Tc(I)]⁺ core to obtain [^99mTc]Tc-CN4NF and [^99mTc]Tc-CN5NF. These compounds were produced in high radiolabeling yields and showed hydrophilicity and good stability in vitro. The bacterial binding assay indicated that [^99mTc]Tc-CN4NF and [^99mTc]Tc-CN5NF were specific to bacteria. Compared with [^99mTc]Tc-CN4NF, biodistribution studies of [^99mTc]Tc-CN5NF showed a higher uptake in bacteria-infected tissues than in turpentine-induced abscesses, indicating that [^99mTc]Tc-CN5NF could distinguish bacterial infection from sterile inflammation. In addition, [^99mTc]Tc-CN5NF had higher abscess/blood and abscess/muscle ratios. SPECT image of [^99mTc]Tc-CN5NF showed that there was a clear accumulation in the infection site, suggesting that it could be a potential bacterial infection imaging radiotracer.